T follicular helper cells: linking cancer immunotherapy and immune-related adverse events.

Journal for Immunotherapy of Cancer
Dirk Baumjohann, Peter Brossart

Abstract

Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4+ T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in...Continue Reading

References

Jun 20, 2013·The Journal of Clinical Investigation·Chunyan Gu-TrantienKaren Willard-Gallo
May 6, 2017·Nature Medicine·Carl H JuneJeffrey A Bluestone
May 3, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter Brossart
Sep 10, 2020·Journal for Immunotherapy of Cancer·Santiago Sánchez-AlonsoArantzazu Alfranca

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